Comparison of zonisamide with non-levodopa, anti-Parkinson's disease drugs in the incidence of Parkinson's disease-relevant symptoms.

INTRODUCTION: Patients with Parkinson's disease (PD) experience various symptoms, both from the disease progression itself and the medication. Few large-scale studies have investigated the associations between zonisamide and these symptoms. This study compared zonisamide and other anti-PD drugs by analyzing their associations with the incidence of PD-relevant symptoms. METHODS: This was a cohort study based on claims data from Diagnosis Procedure Combination hospitals between 2008 and 2014 in Japan. Patients were included in the cohort if they were diagnosed with PD, aged ≥40 years, and were prescribed anti-PD drugs from the same single class without switching to/combination use with other classes excepting levodopa. The outcomes were the incidence of PD-relevant symptoms from the following categories; mental/psychiatric, autonomic nervous system, motor-related, and gastric symptoms. The associations between the incidence of these symptoms and the prescriptions of 8 different classes of anti-PD drugs were explored by the survival analysis. RESULTS: In the final cohort, 9157 patients were included. The zonisamide use was significantly associated with a lower risk of dementia, insomnia, and gastric ulcers than 3 of 7 other classes without levodopa (p < .05). CONCLUSION: There may be a potential clinical impact of zonisamide on some of the PD-relevant symptoms.

One year safety and efficacy of inosine to increase the serum urate level for patients with Parkinson's disease in Japan.

BACKGROUND: Epidemiological studies have repeatedly reported that increased serum urate level is associated with a slower progress of Parkinson's disease (PD). The urate precursor, inosine, raises the serum urate level and is therefore a candidate for a disease modifying treatment. However, an elevated serum urate level is a risk factor for gout, urolithiasis, and cardiovascular diseases. Although there have been previous clinical studies, the use of inosine in a clinical setting is still limited, and its safety is unclear, especially in an Asian population. METHODS: We conducted a single-arm, single-center clinical trial to assess the safety of inosine for PD patients with relatively low urate levels. After informed consent, 10 subjects were orally administered inosine to maintain a target urate level between 6.0mg/dl and 8.0mg/dl for one year. All adverse effects were recorded and categorized by severity. Also, the efficacy of using inosine to raise the serum urate level was reported. RESULTS: We did not observe any adverse events requiring termination or reduction of the study drug, although uric acid crystalluria was transiently observed in a single subject. An inosine dosage of 1070 (SD=501) mg/day significantly raises the urate level from 3.5 (0.84)mg/dl at baseline to 6.68 (1.11)mg/dl at the 52nd week. CONCLUSIONS: Inosine was safely used for one year and effectively raised urate levels in a small group of subjects. Our study is the first report to use inosine for patients with PD in an Asian population.

Cerebrospinal fluid neopterin, but not osteopontin, is a valuable biomarker for the treatment response in patients with HTLV-I-associated myelopathy.

OBJECTIVE: The concentrations of neopterin and osteopontin in the cerebrospinal fluid (CSF) were measured in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in order to evaluate their utility as biomarkers for the treatment response. METHODS: Seven HAM/TSP patients were treated intravenously with high-dose methylprednisolone (1,000 mg/day) for 3 days. CSF samples were collected before and after the treatment. The neopterin and osteopontin concentrations were determined using high-performance liquid chromatography (HPLC) and an enzyme immunoassay, respectively. The clinical symptoms were evaluated using the Osame Motor Disability Score and the Urinary Disturbance Score. RESULTS: Four out of the seven patients showed an improvement in motor function with the treatment, and were therefore classed as responders. The pre-treatment CSF neopterin concentration exceeded the upper limit of normal in all seven of the patients, and tended to be higher in treatment responders as compared to non-responders. The CSF neopterin concentration was reduced following treatment in all patients. The mean CSF neopterin concentration significantly (p<0.01) decreased following treatment by almost 60% (from 124.1±79.9 nmol/L to 49.2±29.8 nmol/L). The mean CSF osteopontin concentration was significantly (p<0.01) higher in the HAM/TSP patients in comparison to the 18 HTLV-1-seronegative patients who were designated as controls (9.54±4.53 mg/L vs. 3.72±3.04 mg/L). No significant (p=0.47) reduction of the CSF osteopontin concentration was observed following the intravenous administration of high-dose methylprednisolone. CONCLUSION: These results indicate that the CSF neopterin concentration, but not the osteopontin concentration, is a potentially valuable biomarker for monitoring the treatment response in HAM/TSP patients. Furthermore, high pre-treatment CSF neopterin concentrations may be a predictive biomarker for a response to intravenous high-dose methylprednisolone therapy.